Aneurysmal subarachnoid hemorrhage (SAH) accounts for 5-10% of annual stroke cases. 50% of the patients die within 30 days with most deaths occurring within the first 48 hours. Acute brain injury after SAH is ischemic in nature and develops within the first 48 hours with mechanisms that are poorly understood. No effective treatment for it currently exists. We have found structural injury in cerebral microvessels after SAH that could affect their function and contribute to acute ischemia. This study investigates the effect of structural injury on microvessel function and the role of intraluminal platelet aggregation in initiating these events after SAH. In an experimental model of SAH we have found intraluminal platelet aggregation, degradation of collagen IV, the major protein of basal lamina, and activation of vascular collagenases within hours after SAH. This study will test the hypotheses that platelet aggregation: 1. reduces microvascular perfusion and 2. initiates the destruction of perivascular collagen IV and thereby causes local breaches of the blood-brain barrier. SAH will be induced in the rat by endovascular perforation. Cerebral blood flow, blood pressure and intracranial pressure will be continuously recorded. Cerebral microvessels (slOOum) will be examined for perfusion, blood-brain barrier function, platelet aggregation, endothelial injury, matrix metalloproteinase-9 activation, and collagen IV loss during the first 48 hours after SAH. The effect of early pharmacological inhibition of platelet aggregation on microvascular perfusion and structural changes will be investigated. Animal behavior and neurological status will be examined to establish the outcome of this therapy on neural function. The experimental design will focus on four major questions: 1) what is the effect of intraluminal platelet aggregation on microvascular perfusion after SAH?, 2) do intraluminal platelet aggregates act as initiators of basal lamina degradation and blood brain barrier disruption after SAH?, 3) what fine structural changes occur in the microvasculature after SAH?, and 4) does early pharmacological inhibition of platelet aggregation improve neurological outcome? This study will extend our current understanding of early microvascular injury after SAH, and will evaluate the therapeutic potential of post-hemorrhage blockade of platelet aggregation.